In rare cases, it's believed that retroviruses can infect human sperm or egg cells. If this happens, and if the resulting embryo survives, the retrovirus can become a permanent part of the human genome, and be passed down from generation to generation. Scientists estimate that as much as 8 percent of the human genome may be comprised of extinct retroviruses left over from infections that occurred millions of years ago. Yet these sequences of fossilized retrovirus were thought to have no discernible functional value.
"The human genome is filled with retrovirus DNA thought to be no more than fossilized junk," said Luban. "Increasingly, there are indications that these sequences might not be junk. They might play a role in gene expression after all."
An expert in HIV and other retroviruses, Luban and his colleagues were seeking to understand if there was a rationale behind where, in the expansive human genome, retroviruses inserted themselves. Knowing where along the chromosomal DNA retroviruses might attack could potentially lead to the development of drugs that protect against infection; better gene therapy treatments; or novel biomarkers that would predict where a retrovirus would insert itself in the genome, said Luban.
Turning these same techniques on the retrovirus sequences already in the human genome, they discovered a sequence, HERV-H, that appeared to be active. "The sequences weren't making proteins because they had been so disrupted over millions of years, but they were making these long, noncoding RNAs," said Luban.
Specifically, the HERV-H sequence was making abundant amounts of RNA in human embryonic stem cellsand only stem cells. In total, there are more than 1,000 HERV-H retrovirus genomes scattered throughout the human genome. The Luban lab also found high levels of HERV-H RNA in some iPS cells. Other iPS cells, perhaps those lines that were not suffi
|Contact: Jim Fessenden|
University of Massachusetts Medical School